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Tuesday, 29 October 2013

Osteosarcoma - A Small Step Forward?

In the past I have written about Dr Stefano Fais in Italy and his work on the use of anti-acid drugs in relation to cancer, for example here and here.In particular his work using proton pump inhibitors (PPI), some of them over-the-counter drugs, to change the tumour micro-environment shows huge potential for therapeutic benefit to patients. One example of this was work done using lansoprazole and standard chemotherapy to treat pets afflicted with cancer, to quote from my previous article:

...this study uses a cheap and readily available drug that is widely used, thus short circuiting many years of safety testing. It is part of a welcome trend in using existing drugs for tackling cancer and cancer-related conditions – other notable examples include the anti-diabetic drug metformin, beta blockers, celecoxib and aspirin. Finally, as with many of the other off-label drugs listed, the target here isn't cancer cells directly, but the tumour microenvironment. Without a supportive microenvironment, cancer cannot thrive and prosper, which is exactly what we want. In this case, by attacking the microenvironment it means that existing chemotherapy drugs can work more effectively and kill the cancer cells. The hope now is that these results can be replicated in a wide range of human cancers, making them susceptible again to the chemotherapy that all too often stops working.

In a new paper Dr Fais and colleagues report a small clinical trial that combined a PPI drug with the standard treatment for osteosarcoma (the bone cancer that killed my son, George). Now the standard treatment for osteosarcoma is multi-drug chemotherapy followed by surgical resection of the bone tumour. A key prognostic marker for this treatment is to look at the degree of cancer cell death in the tumour after it has been removed. A good response is normally when there is greater than 90% tumour necrosis, less than 90% is counted as a poor response to the chemotherapy. So, for this trial Dr Fais and colleagues added pre-treatment with the anti-acid drug Esomeprazole to the standard four drug chemotherapy treatment for osteosarcoma.

The results show that there was a higher rate of good responses in patients taking the esomeprazole prior to chemotherapy compared to historical controls. In the case of the chondroblastic subtype of osteosarcoma the difference in the number of good responders is truly striking. Overall though across all types of osteosarcomas the difference was 47% good responders in the control group versus 57% in the PPI group.

This was a small study, not randomised (due to the fact that osteosarcoma is a relatively rare cancer), and it was looking at response to chemotherapy and not overall survival, but with those caveats this is an important step forward. It adds significantly to the evidence that adding PPI to existing treatments can have positive effects. And, in terms of osteosarcoma, it shows that there is something that can be done to incrementally improve treatments for a disease that remains stubbornly hard to treat.